Regulation of cell volume via microvillar ion channels

Abstract

A novel mechanism of cellular volume regulation is presented, which ensues from the recently introduced concept of transport and ion channel regulation via microvillar structures (Lange K, 1999, J Cell Physiol 180:19-35). According to this notion, the activity of ion channels and transporter proteins located on microvilli of differentiated cells is regulated by changes in the structural organization of the bundle of actin filaments in the microvillar shaft region. Cells with microvillar surfaces represent two-compartment systems consisting of the cytoplasm on the one side and the sum of the microvillar tip (or, entrance) compartments on the other side. The two compartments are separated by the microvillar actin filament bundle acting as diffusion barrier ions and other solutes. The specific organization of ion and water channels on the surface of microvillar cell types enables this two-compartment system to respond to hypo- and hyperosmotic conditions by activation of ionic fluxes along electrochemical gradients. Hypotonic exposure results in swelling of the cytoplasmic compartment accompanied by a corresponding reduction in the length of the microvillar diffusion barrier, allowing osmolyte efflux and regulatory volume decrease (RVD). Hypertonic conditions, which cause shortening of the diffusion barrier via swelling of the entrance compartment, allow osmolyte influx for regulatory volume increase (RVI). Swelling of either the cytoplasmic or the entrance compartment, by using membrane portions of the microvillar shafts for surface enlargement, activates ion fluxes between the cytoplasm and the entrance compartment by shortening of microvilli. The pool of available membrane lipids used for cell swelling, which is proportional to length and number of microvilli per cell, represents the sensor system that directly translates surface enlargements into activation of ion channels. Thus, the use of additional membrane components for osmotic swelling or other types of surface-expanding shape changes (such as the volume-invariant cell spreading or stretching) directly regulates influx and efflux activities of microvillar ion channels. The proposed mechanism of ion flux regulation also applies to the physiological main functions of epithelial cells and the auxiliary action of swelling-induced ATP release. Furthermore, the microvillar entrance compartment, as a finely dispersed ion-accessible peripheral space, represents a cellular sensor for environmental ionic/osmotic conditions able to detect concentration gradients with high lateral resolution. Volume regulation via microvillar surfaces is only one special aspect of the general property of mechanosensitivity of microvillar ionic pathways.

Intracellular delivery of 2-deoxy-D-glucose into tumor cells by long-term cultivation and through swelling-activated pathways: implications for radiation treatment

“…After the fast initial swelling in hypotonic sucrose-substituted medium, all the cell types underwent a regulatory volume decrease (RVD), during which they shrank gradually, recovering their original isotonic volume (Ó 0 ) withiñ 10-15 min despite persisting hypotonicity. RVD involves the release of cytosolic solutes through swelling-activated membrane pathways along with osmotically-driven water loss, which allows the cells to recover their original isotonic volume (19,26,27). In agreement with our findings for two glioblastoma lines (U87 and GaMG), other glioma cells (including the D54-MG line and primary glioma cells from patient biopsies) are able to quickly readjust their volume in anisotonic media via several mechanisms, including chloride pathways and water channels (aquaporins) (28,29).…”

hCLCA1 and mCLCA3 Are Secreted Non-integral Membrane Proteins and Therefore Are Not Ion Channels

“…Electron microscopic examination of surface immunolabeled HEK-hCLCA1 cells showed that this residual hCLCA1 was localized to the microvilli. This is in keeping with an association with ion channels because microvilli are highly specialized regions of the plasma membrane, in which ion channels and transporter proteins are known to reside (48). mCLCA1 has been shown to directly interact with the large conductance potassium channel ␤-subunit KCNMB1 when co-expressed in HEK293 cells.…”

Cellular target of weak magnetic fields: ionic conduction along actin filaments of microvilli

“…Rapid equilibration of the ionic conditions between the internal tip compartment of microvilli and the external medium is one of the consequences following from the presence of cation and anion channels in the microvillar tip membrane and the existence of a cytoskeletal diffusion barrier between tip compartment and cytoplasm (as discussed in Ref. 46). Thus the main conclusion from the findings of Lumpkin and Hudspeth (59) should be that regulation of ion fluxes does not occur at the channel protein itself.…”

“…1) Membrane stress generated during hyposmotic cell swelling shortens microvilli, thereby activating regulatory K ϩ and Cl Ϫ efflux (46). 2) Exposure to lipophilic compounds alters physical properties of the plasma membrane (17,18), giving rise to dissociation of the bindings between membrane and cytoskeleton in microvilli.…”